Fig. (4).

Pharmacological validation of MPEP and alloswitch-1 binding mode. Concentration-response curves of quisqualate (Red), MPEP (Blue) and alloswitch-1 (Green) in (A) wild-type rat mGlu5 receptors, (B) Q646A (equivalent to Q647A in human mGlu5) or (C) P654M (equivalent to P655M in human mGlu5) mutated rat mGlu5 receptors. MPEP and alloswitch-1 activities were evaluated in the presence of 30 nM of quisqualate. HEK293 cells were transiently transfected with the mGlu5 receptor constructs. Receptor activation following stimulation by different concentrations of ligands was determined by IP1 production (see methods). Each data point corresponds to means ± SEM of at least 3 experiments performed in triplicate.